A Review of the Dual Role of MicroRNA-۲۱ in Cardiovascular Diseases

Introduction: Cardiovascular diseases (CVD) are one of the main causes of mortality worldwide, and despitesignificant advancements in cardiovascular research, CVD incidence has significantly increased in recentdecades. Increasing evidence has shown that altered expression patterns of microRNAs (miRs) are linked tocardiovascular system development. The present review attempts to summarize the available literature on therole of miR-۲۱ family members as prognostic, diagnostic, and therapeutic biomarkers in different CVDs.Methods: We performed a comprehensive search of the literature of ۵ online medical databases: GoogleScholar, PubMed, Scopus, Science Direct and Web of Science to identify the related articles and data. Thesearch was conducted using the following search terms: (“Cardiovascular diseases” OR “Heart disease”) AND(“miR-۲۱ family” OR “MicroRNA-۲۱”). In-Silico studies, review articles and articles in any language exceptEnglish were excluded. After the removal of duplicates or irrelevant papers, a thorough examination of the titlesand abstracts was carried out by two different researchers. Then, the full-text was read and the eligible referenceswere also determined. Any disagreements were discussed and agreed upon.Results: To thoroughly summarize miR-۲۱ role in CVDs, we explored more than ۳۰۰ primary research articles.After eliminating irrelevant papers, a total of ۹۷ articles were found relevant and fit into the criteria. Mostinvestigations highlighted miR-۲۱ cardioprotective function in heart injury. Several signaling pathways(PI۳K/Akt, FGFR۱/FGF۲۱/PPAR?, ...) and molecular targets (B cell translocation gene ۲, Phosphatase andtensin homolog, Sprouty۱ and ۲, ...) were reported to be controlled, at least partially, by miR۲۱ and are linkedto CVD pathogenesis. In contrast, some other studies showed that this miR is elevated in the serum/tissue ofCVDs patients, promoting fibrosis and cardiac dysfunction. This dual role can be explained by miR-۲۱s' diverseregulatory functions depending on the microenvironment and cell type within the heart.Conclusion: MiR-۲۱ plays an important role in different CVD-associated pathways and has appeared as apromising cardioprotective agent. However, miR-۲۱s clinical application is restricted due to limited humanexperiments and further investigations are required to address questions regarding miR-۲۱ role against CVDs